Proton magnetic resonance spectroscopy in subjects with high genetic risk of schizophrenia: Investigation of anterior cingulate, dorsolateral prefrontal cortex and thalamus

Objective: Reduced N-acetylaspartate levels in regions of the frontal cortex, including the anterior cingulate cortex, dorsolaterail prefrontal cortex, and thalamus, involved in the pathophysiology of schizophrenia suggest that brain metabolite abnormalities may be a marker of genetic vulnerability to schizophrenia. We used proton magnetic resonance spectroscopy (H-MRS) to acquire absolute concentrations of brain metabolites in subjects with a high genetic risk of schizophrenia to investigate the potential relationship between unexpressed genetic liability to schizophrenia and neuronal dysfunction. Method: Included in the study were 22 subjects who had at least two relatives with schizophrenia (high genetic risk group) and 22 controls with no second-degree relatives with schizophrenia. Absolute concentrations of N-acetylaspartate, creatine, choline, glutamate/glutamine, and myo-inositol and the ratios of metabolites in the anterior cingulate cortex, left dorsolateral prefrontal cortex, and left thalamus were measured using H-MRS at 1.5 Tesla. Results: Relative to the controls, the high genetic risk group showed significant differences in absolute metabolite levels in the spectra of the regions of the left thalamus, including significant decreases in N-acetylaspartate, creatine, and choline concentrations. Conclusions: The study points to neuronal dysfunction, and in particular thalamic dysfunction, as a key region of the vulnerability marker of schizophrenia. Further studies should examine the nature of the thalamus more intensively to further our understanding of thalamic dysfunction as a vulnerability marker.Purdon SE, 2008, SCHIZOPHR RES, V99, P218, DOI 10.1016/j.schres.2007.11.028Lee SJ, 2008, PSYCHOPATHOLOGY, V41, P236, DOI 10.1159/000125557Harms MP, 2007, J NEUROSCI, V27, P13835, DOI 10.1523/JNEUROSCI.2571-07.2007Lymer GKS, 2006, NEUROIMAGE, V33, P275, DOI 10.1016/j.neuroimage.2006.06.031Jessen F, 2006, SCHIZOPHR RES, V87, P81, DOI 10.1016/j.schres.2006.06.011McDonald C, 2006, AM J PSYCHIAT, V163, P478Steen RG, 2005, NEUROPSYCHOPHARMACOL, V30, P1949, DOI 10.1038/sj.npp.1300850Keshavan MS, 2005, SCHIZOPHR RES, V79, P45, DOI 10.1016/j.schres.2005.07.004Whalley HC, 2005, BRAIN, V128, P2097, DOI 10.1093/brain/awh556Jou RJ, 2005, SCHIZOPHR RES, V75, P309, DOI 10.1016/j.schres.2004.11.008Jang DP, 2005, MAGNET RESON MED, V53, P708, DOI 10.1002/mrm.20387Preuss UW, 2005, SCHIZOPHR RES, V73, P91, DOI 10.1016/j.schres.2004.09.019Brewer WJ, 2005, AM J PSYCHIAT, V162, P71McIntosh AM, 2004, BIOL PSYCHIAT, V56, P544, DOI 10.1016/j.biopsych.2004.07.020Theberge J, 2004, PSYCHIAT RES-NEUROIM, V131, P107, DOI 10.1016/j.pscychresns.2004.04.002Tibbo P, 2004, AM J PSYCHIAT, V161, P1116Hazlett EA, 2004, AM J PSYCHIAT, V161, P305Gaser C, 2004, AM J PSYCHIAT, V161, P154Job DE, 2003, SCHIZOPHR RES, V64, P1, DOI 10.1016/S0920-9964(03)00158-0Gruber S, 2003, INVEST RADIOL, V38, P403, DOI 10.1097/01.rli.0000073446.43445.20Baslow MH, 2003, NEUROCHEM RES, V28, P941Bertolino A, 2003, BIOL PSYCHIAT, V53, P906Yoon U, 2003, ANN BIOMED ENG, V31, P441, DOI 10.1114/1.1557973Keshavan MS, 2003, MOL PSYCHIATR, V8, P316, DOI 10.1038/sj.mp.4001325Wood SJ, 2003, SCHIZOPHRENIA BULL, V29, P831Johnstone EC, 2002, AM J MED GENET, V114, P906, DOI 10.1002/ajmg.10304Bjartmar C, 2002, ANN NEUROL, V51, P51, DOI 10.1002/ana.10052Bustillo JR, 2002, AM J PSYCHIAT, V159, P130YUNG A, 2002, COMPREHENSIVE ASSESSCAHN W, 2002, BR J PSYCHIAT S, V43, pS66Arnold DL, 2001, ANN NEUROL, V50, P823Auer DP, 2001, SCHIZOPHR RES, V52, P87Lawrie SM, 2001, BIOL PSYCHIAT, V49, P811Moreno A, 2001, J NEUROCHEM, V77, P347Callicott JH, 2000, AM J PSYCHIAT, V157, P1646Block W, 2000, NEUROSCI LETT, V289, P147Omori M, 2000, PSYCHIAT RES-NEUROIM, V98, P155Blennow K, 2000, J NEURAL TRANSM, V107, P1085Bertolino A, 2000, AM J PSYCHIAT, V157, P26Seidman LJ, 1999, BIOL PSYCHIAT, V46, P941Bertolino A, 1999, EUR J RADIOL, V30, P132Crespo-Facorro B, 1999, AM J PSYCHIAT, V156, P386Pfefferbaum A, 1999, MAGNET RESON MED, V41, P276Cecil KM, 1999, NEUROPSYCHOPHARMACOL, V20, P131Lawrie SM, 1999, LANCET, V353, P30Staal WG, 1998, AM J PSYCHIAT, V155, P1784Callicott JH, 1998, BIOL PSYCHIAT, V44, P941Kegeles LS, 1998, BIOL PSYCHIAT, V44, P382Heimberg C, 1998, PSYCHIAT RES-NEUROIM, V83, P105Keshavan MS, 1997, PROG NEURO-PSYCHOPH, V21, P1285Bertolino A, 1996, AM J PSYCHIAT, V153, P1554Buchsbaum MS, 1996, AM J PSYCHIAT, V153, P191TSAI GC, 1995, PROG NEUROBIOL, V46, P531NURNBERGER JI, 1994, ARCH GEN PSYCHIAT, V51, P849NURNBERGER JI, 1994, ARCH GEN PSYCHIAT, V51, P863PROVENCHER SW, 1993, MAGNET RESON MED, V30, P672BRAND A, 1993, DEV NEUROSCI-BASEL, V15, P289URENJAK J, 1993, J NEUROSCI, V13, P981BRAFF DL, 1993, SCHIZOPHRENIA BULL, V19, P2331